Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography.

OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities. CONCLUSION: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone. CLINICAL RELEVANCE STATEMENT: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic. KEY POINTS: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders.

Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium.

OBJECTIVES: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). PURPOSE: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. METHODS: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard. RESULTS: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). CONCLUSIONS: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD. KEY POINTS: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.

Clinical Value of Information Entropy Compared with Deep Learning for Ultrasound Grading of Hepatic Steatosis.

Entropy is a quantitative measure of signal uncertainty and has been widely applied to ultrasound tissue characterization. Ultrasound assessment of hepatic steatosis typically involves a backscattered statistical analysis of signals based on information entropy. Deep learning extracts features for classification without any physical assumptions or considerations in acoustics. In this study, we assessed clinical values of information entropy and deep learning in the grading of hepatic steatosis. A total of 205 participants underwent ultrasound examinations. The image raw data were used for Shannon entropy imaging and for training and testing by the pretrained VGG-16 model, which has been employed for medical data analysis. The entropy imaging and VGG-16 model predictions were compared with histological examinations. The diagnostic performances in grading hepatic steatosis were evaluated using receiver operating characteristic (ROC) curve analysis and the DeLong test. The areas under the ROC curves when using the VGG-16 model to grade mild, moderate, and severe hepatic steatosis were 0.71, 0.75, and 0.88, respectively; those for entropy imaging were 0.68, 0.85, and 0.9, respectively. Ultrasound entropy, which varies with fatty infiltration in the liver, outperformed VGG-16 in identifying participants with moderate or severe hepatic steatosis (p < 0.05). The results indicated that physics-based information entropy for backscattering statistics analysis can be recommended for ultrasound diagnosis of hepatic steatosis, providing not only improved performance in grading but also clinical interpretations of hepatic steatosis.

Cutoff Values of Acoustic Radiation Force Impulse Two-Location Measurements in Different Etiologies of Liver Fibrosis.

BACKGROUND: Acoustic radiation force impulse (ARFI) imaging is a popular modality to measure liver fibrosis. ARFI selects optimal locations for measurement under imaging guiding. However, there are concerns on study locations and observers bias. To decrease the variations, ARFI at two locations was measured with standardized protocol. This study attempted to establish its cutoff values according to Metavir fibrosis score in different etiologies. METHODS: A consecutive series of patients who received liver histology study were prospectively enrolled. All cases had hemogram, liver biochemistry, viral markers, and ARFI two-location measurements within 4 weeks of histology study. A standardized protocol was performed by single technologist. We excluded patients with alanine aminotransferase >5x upper limit normal. RESULTS: Five hundred and ten patients that included 153 seronegative for both HBsAg and anti-HCV Non-B non-C (NBNC), 33 autoimmune liver diseases (AILD), 261 chronic hepatitis B (CHB), and 63 chronic hepatitis C (CHC) were enrolled. About 83% of NBNC patients had fat cell >5%. For diagnosis of liver cirrhosis, the area under receiver operating characteristic curve of NBNC, AILD, CHB, and CHC groups was 0.937, 0.929, 0.784, and 0.937; the cutoff values for mean ARFI were 1.788, 2.095, 1.455, and 1.710 m/s, respectively. The sensitivity and specificity are both over 0.818 for patients with nonalcoholic fatty liver diseases, CHC, and AILD, but the corresponding data are only 0.727-0.756 in CHB. The Fibrosis-4 Score is as good as ARFI on fibrosis assessment in NBNC. CONCLUSION: The performance of ARFI two-location measurement is excellent in NBNC, AILD, and CHC, but is only satisfactory in CHB.

Correction to: Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

OBJECTIVES: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma: common cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall.

AIMS: To characterize the clinicopathological and genetic features of pleomorphic mantle cell lymphoma (PMCL), which morphologically mimics diffuse large B cell lymphoma (DLBCL). METHODS AND RESULTS: We screened systematically 500 B cell lymphomas morphologically compatible with DLBCL using an immunohistochemical algorithm of three markers (CD5, cyclin D1 and SOX11). Ten cases of PMCL were identified for further study and, surprisingly, four (40%) of them were cyclin D1-negative. These 10 patients were mainly elderly males with advanced disease, and their median survival was only 11 months. All cyclin D1-positive PMCLs tested showed an IGH-CCND1 translocation, whereas one of the four cyclin D1-negative PMCLs had a translocation involving CCND2 and a high CCND2 mRNA level (P < 0.000001). The genomewide copy number profiles of both cyclin D1-positive and cyclin D1-negative PMCLs were similar to those of classical mantle cell lymphoma (MCL) reported previously, confirming the diagnosis. Secondary genetic alterations involved in oncogenic pathways of MCL were observed more frequently in these PMCLs, possibly decreasing the dependence on the driving CCND1 translocation and accounting for the common cyclin D1 negativity. Copy number gains of PIK3CA and CCDC50 were detected in all cyclin D1-negative PMCLs but in only 40% of the cyclin D1-positive PMCLs. These additional oncogenic signals may compensate for the common absence of CCND2 translocation in cyclin D1-negative PMCL. CONCLUSION: We demonstrate for the first time that cyclin D1 negativity is surprisingly common in PMCL morphologically mimicking DLBCL, and the use of a simple immunohistochemical algorithm can prevent misclassification and inappropriate treatment.

A Computer-Aided Diagnosis Scheme For Detection Of Fatty Liver In Vivo Based On Ultrasound Kurtosis Imaging.

Fatty liver disease is a common disease caused by alcoholism, obesity, and diabetes, resulting in triglyceride accumulation in hepatocytes. Kurtosis coefficient, a measure of the peakedness of the probability distribution, has been applied to the analysis of backscattered statistics for characterizing fatty liver. This study proposed ultrasound kurtosis imaging as a computer-aided diagnosis (CAD) method to visually and quantitatively stage the fatty liver. A total of 107 patients were recruited to participate in the experiments. The livers were scanned using a clinical ultrasound scanner with a 3.5-MHz curved transducer to acquire the raw ultrasound backscattered signals for kurtosis imaging. The kurtosis image was constructed using the sliding window technique. Experimental results showed that kurtosis imaging has the ability to visualize and quantify the variation of backscattered statistics caused by fatty infiltration. The kurtosis coefficient corresponding to liver parenchyma decreased from 5.41 ± 0.89 to 3.68 ± 0.12 with increasing the score of fatty liver from 0 (normal) to 3 (severe), indicating that fatty liver reduces the degree of peakedness of backscattered statistics. The best performance of kurtosis imaging was found when discriminating between normal and fatty livers with scores ≥1: the area under the curve (AUC) is 0.92 at a cutoff value of 4.36 (diagnostic accuracy =86.9 %, sensitivity =86.7 %, specificity =87.0 %). The current findings suggest that kurtosis imaging may be useful in designing CAD tools to assist in physicians in early detection of fatty liver.

Differences in liver fibrosis between patients with chronic hepatitis B and C: evaluation by acoustic radiation force impulse measurements at 2 locations.

OBJECTIVES: The purpose of this study was to evaluate liver fibrosis by acoustic radiation force impulse (ARFI) measurements at 2 locations in patients with chronic hepatitis B and C. METHODS: A total of 204 consecutive patients (146 male and 58 female) with chronic hepatitis B (n = 121) and C (n = 83) who underwent liver biopsy were enrolled. All patients received ARFI measurements at 2 locations in the right intercostal space on the same day as biopsy. RESULTS: There was no difference in median ARFI values between detection locations. However, a significant difference was found for low and high values between locations (median ± SD, 1.38 ± 0.43 versus 1.56 ± 0.55 m/s; P < .001). By receiver operating characteristic (ROC) curve analysis for a METAVIR fibrosis score of F4 (cirrhosis), the lower value of 2 measurements had the highest area under the ROC curve (0.750), followed by the mean value (0.744) and the higher value (0.730). Patients with hepatitis C had a higher area under the ROC curve than patients with hepatitis B (0.824 versus 0.707) for predicting liver cirrhosis. By logistic regression analysis, ARFI was the best modality for predicting liver cirrhosis in hepatitis C, and conventional sonography was the best modality in hepatitis B (P < .001). The ARFI value in patients with hepatitis B was significantly influenced by liver inflammation (P = .019). CONCLUSIONS: Acoustic radiation force impulse imaging is the modality of choice for predicting liver cirrhosis in chronic hepatitis C, whereas conventional sonography is still the modality of choice in chronic hepatitis B.

Diagnostic performance of dual-energy contrast-enhanced subtracted mammography in dense breasts compared to mammography alone: interobserver blind-reading analysis.

PURPOSE: To analyse the accuracy of dual-energy contrast-enhanced spectral mammography in dense breasts in comparison with contrast-enhanced subtracted mammography (CESM) and conventional mammography (Mx). MATERIALS AND METHODS: CESM cases of dense breasts with histological proof were evaluated in the present study. Four radiologists with varying experience in mammography interpretation blindly read Mx first, followed by CESM. The diagnostic profiles, consistency and learning curve were analysed statistically. RESULTS: One hundred lesions (28 benign and 72 breast malignancies) in 89 females were analysed. Use of CESM improved the cancer diagnosis by 21.2 % in sensitivity (71.5 % to 92.7 %), by 16.1 % in specificity (51.8 % to 67.9 %) and by 19.8 % in accuracy (65.9 % to 85.8 %) compared with Mx. The interobserver diagnostic consistency was markedly higher using CESM than using Mx alone (0.6235 vs. 0.3869 using the kappa ratio). The probability of a correct prediction was elevated from 80 % to 90 % after 75 consecutive case readings. CONCLUSION: CESM provided additional information with consistent improvement of the cancer diagnosis in dense breasts compared to Mx alone. The prediction of the diagnosis could be improved by the interpretation of a significant number of cases in the presence of 6 % benign contrast enhancement in this study. KEY POINTS: • DE-CESM improves the cancer diagnosis in dense breasts compared with mammography. • DE-CESM shows greater consistency than mammography alone by interobserver blind reading. • Diagnostic improvement of DE-CESM is independent of the mammographic reading experience.

A survey of the current status of coronary CT angiography using 64-slice multidetector CT in Taiwan.

BACKGROUND/PURPOSE: The 64-slice multidetector CT (64-MDCT) has bolstered the sensitivity and specificity of coronary CT angiography (CCTA) for detecting coronary artery disease. We performed this study to understand the current status of CCTA using 64-MDCT, so as to determine further promotion and optimal regulation schemes of CCTA in Taiwan. METHODS: Information about CCTA from 68 domestic hospitals with 64-MDCT was collected by means of a questionnaire from July 2009 to January 2010. The studied details included: (1) the implementation background of CCTA; (2) the interdisciplinary cooperation and report processing of CCTA; and (3) the promotion strategy of CCTA. RESULTS: The majority of CCTA sites (89.7%) were administered by diagnostic radiologists. Most cardiologists and cardiac surgeons have confirmed its clinical value by referring patients to undergo CCTA. Of the CCTA reports by radiologists, 41.2% had their report supplemented by referring cardiologists. Such cooperation amongst specialists promoted the development of CCTA. Of CCTA studies, 89.7% included coronary calcium scoring. Most (60.3%) respondents asserted the cost of a study to be 15,000 to 20,000 new Taiwan dollars. Nearly two-fifths (41.2%) of the respondents supported the restriction of subjects for CCTA to those who were high risk group for coronary artery disease or those > 40 years of age. CONCLUSION: Diagnostic radiologists are primarily in charge of managing CCTA sites in Taiwan. The interdisciplinary cooperation amongst radiologists and cardiologists in reporting CCTA may expedite the development of CCTA. The domestic radiologists are expected to standardize the process, which includes interpreting and reporting CCTA findings.

The Role of Artificial Intelligence in Coronary Calcium Scoring in Standard Cardiac Computed Tomography and Chest Computed Tomography With Different Reconstruction Kernels.

PURPOSE: To assess the correlation of coronary calcium score (CS) obtained by artificial intelligence (AI) with those obtained by electrocardiography gated standard cardiac computed tomography (CCT) and nongated chest computed tomography (ChCT) with different reconstruction kernels. PATIENTS AND METHODS: Seventy-six patients received standard CCT and ChCT simultaneously. We compared CS obtained in 4 groups: CS CCT , by the traditional method from standard CCT, 25 cm field of view, 3 mm slice thickness, and kernel filter convolution 12 (FC12); CS AICCT , by AI from the standard CCT; CS ChCTsoft , by AI from the non-gated CCT, 40 cm field of view, 3 mm slice thickness, and a soft kernel FC02; and CS ChCTsharp , by AI from CCT image with same parameters for CS ChCTsoft except for using a sharp kernel FC56. Statistical analyses included Spearman rank correlation coefficient (ρ), intraclass correlation (ICC), Bland-Altman plots, and weighted kappa analysis (κ). RESULTS: The CS AICCT was consistent with CS CCT (ρ = 0.994 and ICC of 1.00, P < 0.001) with excellent agreement with respect to cardiovascular (CV) risk categories of the Agatston score (κ = 1.000). The correlation between CS ChCTsoft and CS ChCTsharp was good (ρ = 0.912, 0.963 and ICC = 0.929, 0.948, respectively, P < 0.001) with a tendency of underestimation (Bland-Altman mean difference and 95% upper and lower limits of agreements were 329.1 [-798.9 to 1457] and 335.3 [-651.9 to 1322], respectively). The CV risk category agreement between CS ChCTsoft and CS ChCTsharp was moderate (κ = 0.556 and 0.537, respectively). CONCLUSIONS: There was an excellent correlation between CS CCT and CS AICCT , with excellent agreement between CV risk categories. There was also a good correlation between CS CCT and CS obtained by ChCT albeit with a tendency for underestimation and moderate accuracy in terms of CV risk assessment.

Ultrasonography of acute retroperitoneum.

The retroperitoneum is an important space in the human body that is often implicated in a range Epub ahead of print of acute medical conditions, some of which can be life-threatening. Ultrasonography may serve as a pivotal first-line imaging technique when assessing patients with suspected retroperitoneal abnormalities. Effective ultrasonography of the retroperitoneum requires a comprehensive grasp of its anatomy, adjacent structures, and potential pathologies. Being well-acquainted with the imaging characteristics of acute conditions can meaningfully assist in an accurate diagnosis and guide subsequent management. This review article summarizes and illustrates the acute conditions involving the retroperitoneum through the lens of ultrasound imaging.

Hyperpolarized Carbon-13 Magnetic Resonance Imaging: Technical Considerations and Clinical Applications.

Hyperpolarized (HP) carbon-13 (13C) MRI represents an innovative approach for noninvasive, real-time assessment of dynamic metabolic flux, with potential integration into routine clinical MRI. The use of [1-13C]pyruvate as a probe and its conversion to [1-13C]lactate constitute an extensively explored metabolic pathway. This review comprehensively outlines the establishment of HP 13C-MRI, covering multidisciplinary team collaboration, hardware prerequisites, probe preparation, hyperpolarization techniques, imaging acquisition, and data analysis. This article discusses the clinical applications of HP 13C-MRI across various anatomical domains, including the brain, heart, skeletal muscle, breast, liver, kidney, pancreas, and prostate. Each section highlights the specific applications and findings pertinent to these regions, emphasizing the potential versatility of HP 13C-MRI in diverse clinical contexts. This review serves as a comprehensive update, bridging technical aspects with clinical applications and offering insights into the ongoing advancements in HP 13C-MRI.

Incidental Findings in Lung Cancer Screening.

While low-dose computed tomography (LDCT) for lung cancer screening (LCS) has been recognized for its effectiveness in reducing lung cancer mortality, it often simultaneously leads to the detection of incidental findings (IFs) unrelated to the primary screening indication. These IFs present diagnostic and management challenges, potentially causing unnecessary anxiety and further invasive diagnostic procedures for patients. This review article provides an overview of IFs encountered in LDCT, emphasizing their clinical significance and recommended management strategies. We categorize IFs based on their anatomical locations (intrathoracic-intrapulmonary, intrathoracic-extrapulmonary, and extrathoracic) and discuss the most common findings. We highlight the importance of utilizing guidelines and standardized reporting systems by the American College of Radiology (ACR) to guide appropriate follow-ups. For each category, we present specific IF examples, their radiologic features, and the suggested management approach. This review aims to provide radiologists and clinicians with a comprehensive understanding of IFs in LCS for accurate assessment and management, ultimately enhancing patient care. Finally, we outline a few key aspects for future research and development in managing IFs.

Three-Tesla Magnetic Resonance Imaging Characteristics of Hypertrophic Cardiomyopathy: A Comparison with Several Echocardiography Parameters.

Background: Hypertrophic cardiomyopathy (HCM) is a primary cardiac disorder characterized by myocardial hypertrophy without increased afterload. This study set out to describe the cardiac magnetic resonance (CMR) imaging characteristics of HCM and to evaluate correlations of selected CMR parameters with echocardiography. Methods: This cross-sectional study enrolled 46 patients diagnosed at the Vietnam Heart Institute with HCM and underwent CMR at the Radiology Center, Bach Mai Hospital, from July 2021 to September 2022. Results: A left ventricular outflow tract (LVOT)/aortic valve (AO) diameter ratio of ≥0.38 on CMR was consistent with an LVOT pressure gradient (PG) of <30 mmHg on echocardiography. The LVOT diameter and the LVOT/AO diameter ratio differed significantly between obstructive and non-obstructive HCM. The predominant phenotypes were diffuse asymmetric HCM (32.6%) and septal HCM (37%), followed by apical HCM (6.5%). Most late gadolinium enhancement (LGE) lesions were observed in the mid-wall of the hypertrophic segments. The mean LGE mass was significantly higher in the obstructive group than in the non-obstructive HCM group (p < 0.05). A strong negative correlation (r = -0.66) was found between the LVOT/AO diameter ratio on the CMR and the LVOT PG via echocardiography. Moreover, echocardiography detected morphologic risk factors for sudden cardiac death (SCD) in 80.4% of patients, whereas the corresponding proportion detected by CMR was 91.3%. Patients with systolic anterior motion (SAM) had a risk for a LVOT/AO diameter ratio <0.38, which was 5.7 times the risk observed in their counterparts without SAM. Conclusions: The LVOT/AO diameter ratio detected by CMR is a precise index for classifying hemodynamic HCM groups. CMR was better than echocardiography for SCD risk stratification.

Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

The effectiveness of coronary computed tomography angiography and functional testing for the diagnosis of obstructive coronary artery disease: results from the individual patient data Collaborative Meta-Analysis of Cardiac CT (COME-CCT).

AIM: To determine the effectiveness of functional stress testing and computed tomography angiography (CTA) for diagnosis of obstructive coronary artery disease (CAD). METHODS AND RESULTS: Two-thousand nine-hundred twenty symptomatic stable chest pain patients were included in the international Collaborative Meta-Analysis of Cardiac CT consortium to compare CTA with exercise electrocardiography (exercise-ECG) and single-photon emission computed tomography (SPECT) for diagnosis of CAD defined as ≥ 50% diameter stenosis by invasive coronary angiography (ICA) as reference standard. Generalised linear mixed models were used for calculating the diagnostic accuracy of each diagnostic test including non-diagnostic results as dependent variables in a logistic regression model with random intercepts and slopes. Covariates were the reference standard ICA, the type of diagnostic method, and their interactions. CTA showed significantly better diagnostic performance (p < 0.0001) with a sensitivity of 94.6% (95% CI 92.7-96) and a specificity of 76.3% (72.2-80) compared to exercise-ECG with 54.9% (47.9-61.7) and 60.9% (53.4-66.3), SPECT with 72.9% (65-79.6) and 44.9% (36.8-53.4), respectively. The positive predictive value of CTA was ≥ 50% in patients with a clinical pretest probability of 10% or more while this was the case for ECG and SPECT at pretest probabilities of ≥ 40 and 28%. CTA reliably excluded obstructive CAD with a post-test probability of below 15% in patients with a pretest probability of up to 74%. CONCLUSION: In patients with stable chest pain, CTA is more effective than functional testing for the diagnosis as well as for reliable exclusion of obstructive CAD. CTA should become widely adopted in patients with intermediate pretest probability. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Database for Systematic Reviews-CRD42012002780. CRITICAL RELEVANCE STATEMENT: In symptomatic stable chest pain patients, coronary CTA is more effective than functional testing for diagnosis and reliable exclusion of obstructive CAD in intermediate pretest probability of CAD. KEY POINTS: Coronary computed tomography angiography showed significantly better diagnostic performance (p < 0.0001) for diagnosis of coronary artery disease compared to exercise-ECG and SPECT. The positive predictive value of coronary computed tomography angiography was ≥ 50% in patients with a clinical pretest probability of at least 10%, for ECG ≥ 40%, and for SPECT 28%. Coronary computed tomography angiography reliably excluded obstructive coronary artery disease with a post-test probability of below 15% in patients with a pretest probability of up to 74%.